SYNTHETIC BIOLOGY MAY USHER IN A POST-PETROLEUM ERA, BUT IT WON’T BE GREENBy Kathy Jo Wetter

In a classic children's book by Dr. Seuss, wily entrepreneur Sylvester McMonkey McBean persuades the Sneetches, whom he finds playing on the beaches, to pay three dollars each(es) to enter a mysterious-looking machine. McBean promises them they will enter one end of the machine a certain kind of Sneetch and come out the other end a different, better kind of Sneetch. That, in a nutshell, is the sales pitch of biofuel production using synthetic biology. Aristides Patrinos, formerly of the US Department of Energy and now President of Synthetic Genomics, Inc., describes it this way: "The ideal situation would essentially just be one big vat, where in one place you just stick the raw material - it could be switch grass - and out the other end comes fuel."1 Stephen Chu, Nobel laureate and Barack Obama's pick for U.S. Energy Secretary, is also excited by the prospect of the "biorefinery" approach to fuel production using synthetic biology; he calls them "fourth-generation biofuels." In his Senate confirmation hearing on January 13th, Chu enthused about the brilliant scientists who have been able to produce gasoline-like substitutes - not ethanol - directly from simple plant sugars. Now, he says, they're working to scale-up production.

In Dr. Seuss's story, the Sneetches turn out to have been hoodwinked. As McBean drives away surrounded by piles of cash, leaving the Sneetches behind alone on their beaches, he states the lamentable and obvious truth: "You can't teach a Sneetch." It seems we're having trouble learning, too. Recent experience with industrial agrofuels (critics prefer the more precise "agrofuels" to "biofuels" to describe fuels derived from agricultural products) offers a modern day parable about the dangers of techno-fixes that are promoted as green and sustainable solutions to peak oil and climate change. It has become increasingly clear that industrial agrofuels are not a socially or ecologically sustainable response to climate change. Not only are they driving the world's poorest farmers off their land and into deeper poverty, they are competing with food crops and, according to an internal World Bank study, are the single greatest factor contributing to the rise in food prices.2 Oxfam reported in June 2008 that agrofuels have pushed over 30 million people from subsistence to hunger.3 Recent scientific papers conclude that today's industrial agrofuel production actually increases greenhouse gas emissions - contributing to climate change rather than arresting it.4

Now we're being told that synthetic biology is the game-changing solution we need. Advocates assure us that the "food vs. fuel" conundrum will be irrelevant in the future "sugar economy." They say feedstocks for biorefineries will come from cheap and plentiful cellulosic biomass - plant matter composed of cellulose fibers, including crop residues such as rice straw, corn stalks, wheat straw, wood chips, and dedicated "energy crops" such as switch grass, fast-growing (and, eventually, genetically-engineered) trees, even algae. But there are technical barriers. Switch grass, corn stalks and wood chips aren't efficient agrofuel feedstocks for the same reason they aren't good (human) food sources: they are difficult to break down and turn into energy. Only certain microbial enzymes - some of which exist in the guts of ruminants - can digest and process the cellulose and hemicellulose found within the cells of these plants. Another hurdle is high lignin content. Lignin, present to some degree in almost all plants, is responsible for water transport and plays a major role in a plant's ability to sequester carbon. But it's indigestible to enzymes and can be broken down only by certain bacteria and fungi. Synthetic biologists are developing improved "pretreatments" for biomass, including engineered microbes that can more efficiently separate cellulose from lignin and can break down the cellulosic materials for further processing.

But synthetic biologists are focusing most of their attention on the fermentation part of the process, the stage where plant sugars are converted to fuel. Inside a cell, a series of chemical reactions takes place, triggered and regulated by enzymes. The chemical reactions occur sequentially. Imagine a line of dominoes standing on end; knocking down a domino at one end of the line can trigger changes along its entire length. Scientists have figured out how to manipulate a cell's "metabolic pathways" along which chemical reactions take place, in order to alter which chemicals are ultimately produced. By changing the metabolic pathways in microbes such as yeast or E. coli, researchers have been able to "train" them to convert sugar directly into fuels that resemble petrochemicals. The advantage is that fuels produced this way are compatible with existing infrastructure. Theoretically, with enough targeted manipulation, any chemical substance could be produced, not just fuels, but other high-value chemicals, plastics and pharmaceuticals.

Amyris Biotechnologies, a California-based synthetic biology start-up, found the spotlight in 2004 when its high-profile efforts to coax engineered microbes to produce an anti-malarial compound received support from the Bill & Melinda Gates Foundation. Nowadays, the company's primary goal is to modify the metabolic pathways of yeast so that it ferments sugars to produce gasoline, diesel and jet fuel. In 2007, Amyris raised $70 million in venture capital to develop synthetic fuel technology. In April 2008, Amyris announced a joint venture with Brazil's Crystalsev to commercialize "advanced renewable fuels" made from sugarcane.5 Amyris calls the products of its proprietary technology "No Compromise" and describes them as "low cost renewable fuels and chemicals that are intended to be environmentally friendly, compatible with the existing infrastructure, and have performance attributes comparable to petroleum-based fuels."6

No compromise? A post-petroleum era driven by plant-derived fuels may sound fresh and green, but if synthetic biology's fuels are dependent on agricultural biomass, there will be a great deal of compromise involved. What happens when all plant matter becomes a potential feedstock? Who decides what qualifies as agricultural waste or residue? Whose land will grow the feedstocks? Civil society organizations concerned with climate change, agriculture and food policy, human rights and indigenous peoples' rights and biodiversity have vigorously opposed first-generation industrial agrofuels and are voicing concerns over next-generation agrofuels - most recently in an open letter published January 15th, 2009, as a new agrofuel-loving administration comes to power in the U.S. The letter argues that "virtually all of the proposed cellulosic feedstocks...present serious ecological concerns on the scale required to maintain biorefinery operations and significantly contribute to U.S. energy demands."7

The earth's plant biomass is rapidly dwindling. Forests and grasslands, in particular, are disappearing at an alarming rate. Researchers estimate that humans already consume almost a quarter of global biomass (24%).8 Of that amount, more than half (53%) is harvested for food, fuel, heating and lumber, 40% is lost through land use changes, and 7% is burned in human-induced fires.1 The U.S. currently consumes 190 million dry tons of biomass annually for energy, and the government wants to increase that figure to one billion tons. Researchers conclude that the goal is technically feasible, but only by increasing yields of energy crops by 50% and by removing large quantities (~75%) of agricultural residues from cropland.1 Impacts of increased residue removal will include impoverished soils (requiring more industrial fertilizers) and dangerous increases in soil erosion. We will see vast increases in pesticide- and herbicide-use. Removal of dead and dying trees from forests will increase biodiversity losses and decrease forest carbon-sequestration capacity. Additionally, many plants identified as good candidates for second-generation agrofuels are harmful to the environment as invasive species (e.g., miscanthus, switch grass, reed canary grass).1

Some synthetic biologists recognize that fermenting plant sugars is not the best way for society to move beyond petroleum. But we may find ourselves equally disturbed by their proposed alternatives. J. Craig Venter, founder of Synthetic Genomics, Inc., has been researching photosynthetic bacteria to see if he can engineer them to produce fuel directly, using water as a feedstock. "It's infinitely scalable," Venter says.1 Late last year, the World Intellectual Property Organization published a patent application (WO2008143630A2) from the J. Craig Venter Institute for the invention of a "recombinant hydrogen-producing cyanobacterium...useful for generating hydrogen from water." That engineered microbes could wreak havoc if released - intentionally or unintentionally - in the environment is one obvious concern. Venter says he shares the concerns and is working on ways to engineer his microbes so they are not viable in the natural environment. "We should be totally aligned with the environmentalists on this,"1 says Venter, but experience with agricultural biotechnology has shown that a promise of containment is not enough to control genetically modified organisms once they're in farmers' fields. Synthetic biology's living organisms will be no less difficult to contain and control.

Katy Jo Wetter has worked as a researcher with Action Group on Erosion, Technology and Concentration, or ETC Group, since 2001. She holds a Ph.D. from the University of North Carolina at Chapel Hill.

10. U.S. Department of Energy and U.S. Department of Agriculture, Biomass as Feedstock for a Bioenergy and Bioproducts Industry: the Technical Feasibility of a Billion-Ton Annual Supply, April 2005. Online at: http://www1.eere.energy.gov/biomass/pdfs/final_billionton_vision_report2.pdf